Temporal and sequential transcriptional dynamics define lineage shifts in corticogenesis

The cerebral cortex contains billions of neurons, and their disorganization or misspecification leads to neurodevelopmental disorders. Understanding how the plethora of projection neuron subtypes are generated by cortical neural stem cells (NSCs) is a major challenge. Here, we focused on elucidating the transcriptional landscape of murine embryonic NSCs, basal progenitors (BPs), and newborn neurons (NBNs) throughout cortical development. We uncover dynamic shifts in transcriptional space over time and heterogeneity within each progenitor population. We identified signature hallmarks of NSC, BP, and NBN clusters and predict active transcriptional nodes and networks that contribute to neural fate specification. We find that the expression of receptors, ligands, and downstream pathway components is highly dynamic over time and throughout the lineage implying differential responsiveness to signals. Thus, we provide an expansive compendium of gene expression during cortical development that will be an invaluable resource for studying neural developmental processes and neurodevelopmental disorders.

Automated summary

The study reveals dynamic transcriptional changes and heterogeneity within murine embryonic NSCs, BPs, and NBNs. Signature hallmarks of NSC, BP, and NBN clusters were identified, along with predicted active transcriptional nodes and networks contributing to neural fate specification. Expression of receptors, ligands, and downstream pathway components showed highly dynamic changes over time and throughout the lineage, indicating differential responsiveness to signals.